Small proteins in Vibrio cholerae: dual regulators and mediators of phage defense

Dual RNA regulators are a unique group of small regulatory RNAs (sRNAs) that merges base-pairing sRNA function with small protein (SP) encoding function of an mRNA. In the previous decades, the importance of sRNAs has been extensively studied ranging from stress responses, antibiotic tolerance, virulence, carbon metabolism, and microbial communication. In contrast, only little is known about dual RNA regulators and SPs. The problem is mainly due to the small size of SPs (≤ 70 amino acids), poor annotation, and the lack of genetic screens aiming to characterize SPs in bacteria. To address this problem in the major human pathogen Vibrio cholerae, we performed ribosome profiling to identify potential small open reading frames at the genome-wide level. These experiments revealed 75 potential sORFs in V. cholerae, of which we confirmed 44 for in vivo translation by GFP reporter and validated 18 by Western Blotting. Characterization of SPs led us to discover dual-function RNAs pivotal during carbon utilization and small proteins contributing to anti-phage defense systems. My PhD project focuses on uncovering the importance of dual RNA regulators and SPs in bacterial metabolic and environmental adaptation networks.

PhD start: 02/01/2022